This research program is intended to define the protective mechanism(s) of splenectomy against acute tubular necrosis (ATN) which can be produced in dog by constant infusion (i.v.) of epinephrine (Epi) (4 micron/Kg/min) for 6 hours. This ATN, associated with excessive renal congestion and coagulopathy constitute a unique model of the renal lesions found in acute renal failure due to trauma or shock in man. Both acute (post 20-30 minutes) and chronic (post 2-4 weeks) splenectomy prior to i.v. Epi resulted in significant reductions of the frequency and severity of ATN and renal congestion, and also absence of coagulopathy. These aforesaid observations suggest that splenectomy has afforded renal protection via mechanism(s) against inducements of renal congestion and coagulopathy. Studies will be initiated to compare coagulation mechanisms between sham-operated and chronic splenectomized dogs. In both groups, renal blood flow, effective renal plasma flow, glomerular filtration rate, and renal venous pressure will be measured to demonstrate presence or absence of renal failure. Postinfusion follow-up of some dogs from both groups for 3-6 weeks with serial studies of urine output, serum creatinine, coagulation studies, and renal histopathology would allow the establishment of the natural history of epinephrine-induced ATN and the protective effects of splenectomy. In addition, treatment of sham-operated dogs with drugs effective against adrenergic receptors, coagulation, and thrombotic processes before or during Epi infusion would allow us to determine whether the beneficial effect of these drugs against ATN is equivalent to that of splenectomy. Finally, the role of the spleen in the pathogenesis of Epi-induced ATN can be proven or disproven by delivering splenic venous blood obtained from a sham-operated dog during i.v. Epi directly into the systemic circulation of a splenectomy dog.